Why Insulin Signals Aren’t Received

Irene Schauer, MD, PhD

Occupation: Endocrinologist

Focus: Type 1 Diabetes

ADA Research Funding: Junior Faculty Grant

You could call insulin resistance a communication problem. Insulin is a hormone that sends the body signals, telling it to metabolize glucose. When the body stops responding to insulin’s signals—literally resisting the hormone’s orders—it is insulin resistant.

Insulin resistance has long been recognized as an important cause of type 2 diabetes, forcing the body to pump out ever increasing amounts of insulin until the pancreas gives out. New research shows that insulin resistance is a problem for people with type 1 diabetes, too.

“We tend to think of type 1 diabetes as a disease of insulin deficiency, which it is,” says Irene Schauer, an endocrinologist working at the University of Colorado–Denver’s medical school. “But researchers have found that people with type 1 are often significantly insulin resistant.”

The idea that type 1 might bring with it insulin resistance isn’t new. Studies in the early 1980s suggested it might be a problem, but at the time glucose control was the biggest concern. “The goal was to control glucose, and they thought that would take care of everything,” Schauer says. But it looks as if even with better control, some people with type 1 might be insulin resistant.

Schauer found that people with type 1 diabetes had a surprisingly slow reaction to the insulin signals compared with participants without diabetes. “Our study was the first to compare a large number of people with type 1 to a nondiabetic cohort,” she says. “The diabetic group wasn’t overweight, and they had good HDL cholesterol. You would expect them to be more insulin sensitive, but they were twice as resistant as the nondiabetic cohort. So something else must be going on.”

The best guess is that insulin injections just aren’t good enough to replace the body’s natural processes. “We can never replace insulin as well as the pancreas does naturally,” Schauer says. “In normal regulation [of blood glucose], there’s a whole conversation that reflects insulin levels in the liver and the blood. When we give insulin subcutaneously, that conversation doesn’t happen.” The consequences reach far beyond the endocrine system. Schauer suggests that insulin resistance could be responsible for weak or stiff arteries, for example.

Insulin does a lot more in the body than regulate blood sugar levels. It also helps control the opening and closing of arteries and other blood vessels. When it’s absent, or delivered via injection rather than the pancreas, “there’s less of a response to the vascular effects of insulin, too,” Schauer says.

That may be why insulin resistance is a predictor of cardiovascular diseases such as heart attacks and strokes. People with type 1 diabetes are nearly twice as likely to have cardiovascular disease as their counterparts without diabetes. With the help of a grant from the American Diabetes Association, Schauer is working to establish the exact connection: “We’re trying to ask the question directly: If we do target insulin sensitivity, do we see early benefits that might translate to long-term cardiovascular benefits?”

Schauer has enrolled 30 people—15 with type 1 diabetes and 15 without—in a small study to establish a clear link between cardiovascular disease and insulin sensitivity. Using a drug called acipimox, she improves the participants’ insulin sensitivity. Then, using blood tests that look at vascular health and inflammation plus high-tech tools to measure the flexibility of arteries and the heart muscle, she sees if there have been short-term improvements in their cardiovascular function. (Acipimox isn’t a wonder drug: Its ability to improve insulin sensitivity fades after a few weeks.)

The study is a spinoff of a larger study called CACTI, or Coronary Artery Calcification in Type 1 Diabetes. Begun over a decade ago, CACTI has followed more than 1,400 people, half with diabetes and half without, to see the different ways diabetes affects cardiovascular health.

It’s a first step toward unraveling the relationship between insulin resistance and heart health. It’s part of a growing recognition that diabetes is a complex disease, a chain of cause and effect with consequences throughout the body far beyond the basics of blood sugar levels and insulin. “The studies I’m doing are hopefully providing support for the idea,” Schauer says. “Our goal in treating diabetes isn’t just to have a nice pretty number on your chart for blood glucose, but also to treat the complications of diabetes.”

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